Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers

SIMPLE SUMMARY: About 30% of patients with papillary thyroid cancer (PTC) experience persistent/recurrent disease within 10 years after an initial treatment, serum thyroglobulin (Tg) representing the gold standard for surveillance. However, the measurement of serum Tg is unreliable in the presence of anti-thyroglobulin antibodies (TgAb). The aim of this pilot study was to investigate the role of circulating miRNA as valuable biomarkers for the early detection of persistent disease in TgAb-positive PCT patients. In our series, the serum miRNA (221, 222, 375, 155, and 146b) levels were >two-folds higher in the PTC patients than the controls. Moreover, a decrease of 50% or more in circulating miRNAs levels compared to the baseline was observed in patients with an excellent response to therapy but not in those with persistent disease, respectively. Accordingly, serum miRNA kinetics may provide additional and independent information to early detect persistent disease in PTC patients with an uninformative Tg and emerge as a candidate alternative PTC biomarker. ABSTRACT: Background: We aimed to evaluate the role of circulating miRNAs as a biomarker of the persistence of papillary thyroid cancer (PTC) in patients with an “uninformative” thyroglobulin (Tg) measurement. Methods: We prospectively enrolled 49 consecutive PTC patients with Tg-positive antibodies (TgAb) who had undergone a (near)-total thyroidectomy and (131)I therapy (RIT). The serum thyroid stimulating hormone (TSH), Tg, and TgAb levels were measured before and at 6 and 12 months after RIT, respectively. The serum miRNA (221, 222, 375, 155, and 146b) levels were measured simultaneously. Results: The response to the initial therapy was assessed according to the 2015 ATA criteria. A decrease in 50% or more of serum miRNA over time was observed in 41/49 PTC patients, who showed an excellent response (ER), but six and two patients were classified to have an indeterminate/incomplete biochemical or incomplete structural response to initial therapy. Conclusion: Serum miRNA kinetics emerge as a promising biomarker for the early detection of a persistent disease in PTC patients with uninformative Tg results.